Arginine vasopressin (AVP) and related peptides have profound influences on social behaviors in vertebrates, particularly on emotional aggressive and affiliative interactions between individuals. Although we have recently shown that AVP can promote antisocial responses towards same-sex social stimuli in men and affiliative responses towards same-sex social stimuli in women, we do not yet know if there are sexually dimorphic AVP circuits that promote different social responses in the sexes, or rather if AVP's antisocial and affiliative effects depend on social context, specifically whether the social stimulus is male or female. The first aim of this application is therefore to measure the effects of intranasal AVP on emotional responses to same and other sex faces in men and women to see if AVP produces antisocial effects towards males and affiliative effects towards females, or rather if AVP uniformly promotes antisocial responses in males and affiliative responses in females. This will be done by measuring the effects of AVP on somatic responses associated with anger and threat (contractions of the corrugator supercilii) and with affiliation (contractions of the zygomaticus major, which control smiling) when subjects view the faces of same and other sex individuals, and by measuring the effects of AVP on perceptual responses to those faces, particularly on ratings of friendliness / approachability. We will also determine the dose-responsiveness for these effects, and determine if the magnitude of AVP's antisocial and/or affiliative effects depend on background genotype, particularly on allelic variations in the polymorphic RS3 promoter region of the AVP V1a receptor gene. Finally, we will identify regions in the brain where responses to those social stimuli change as a function of AVP administration. Together, these studies will elucidate the context and gender specificity of AVP's effects on emotional social communication in humans, as well as the molecular and neuroanatomical mechanisms associated with those effects. Ultimately, these studies will not only increase our understanding of the neurochemical mechanisms associated with normal social / emotional regulation in humans, but also our understanding of how dysfunctions within one of those systems may contribute to disorders characterized by social / emotional disturbances. PUBLIC HEALTH RELEVANCE: By determining if arginine vasopressin (AVP) can influence emotional social communication in men and women, particularly if it promotes antisocial and/or affiliative responses to social stimuli in men and women, the studies associated with this application will ultimately help us better understand and treat individuals with disorders that affect emotional social regulation, most notably those with autism and/or antisocial personality disorder. In fact, these studies could ultimately help develop pharmacological and/or genetic therapies that could help alleviate some of the otherwise intractable symptoms associated with these disorders.